P1448: LONG-TERM SURVIVORS AFTER FAILURE OF CAR-T CELL THERAPY FOR R/R LARGE B-CELL LYMPHOMA (LBCL): A GLA/DRST STUDY
Authors: P. Derigs, W. Bethge, U. Holtick, B. von Tresckow, F. Ayuk, O. Penack, V. Vucinic, M. von Bonin, C. Baldus, D. Mougiakakos, G. Wulf, U. Schnetzke, M. Stelljes, S. Thomas, R. Schroers, N. Kroeger, P. Dreger
Journal: HemaSphere (2022)

Background: Information on the long-term outcome of patients who relapse or progress after CD19-directed CAR-T therapy with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) for >2L treatment of LBCL is still limited. Aims: The purpose of this study was to investigate characteristics, relapse patterns and management strategies in patients with LBCL surviving one year or longer after having failed a preceding standard of care CAR-T therapy. Methods: The study sample consisted of all patients who had a relapse/progression event in a prior GLA/DRST real world analysis (Bethge et al, ASH 2022 #3822). Baseline patient, disease, and treatment data were collected from MED-A cellular therapy forms. Centers were approached to provide additional treatment and follow-up information for each patient with a documented event. Results: Altogether, relapse/progression (REL) after CAR-T therapy was reported for 214 of 356 patients (60%) of the original study. For 143 of 214 patients (67%) a full dataset as needed for the purpose of this study was available. OS at 12 months post REL of these 143 patients was 22% with no significant difference between axi-cel and tisa-cel failures (Figure). 26 of 143 patients (18%) survived 12 months or longer from REL, 109 (76%) died within the first year after REL, and 8 patients (6%) were alive but had not reached the 12-month landmark. Patients surviving and not surviving 12 months post REL, respectively, were comparable for age, gender, IPI at lymphodepletion, PS, prior HCT, and 1st salvage regimens used. However, long-term survivors had less often bridging failure prior to CAR-T therapy, met less often ineligibility criteria for ZUMA1, had less often REL within the first 30d and more often beyond 100d post CAR-T therapy, and had more often received alloHCT for consolidation of treatment responses post REL (Table). 12-month OS post REL of the 40 patients who proceeded to alloHCT was 34% (19-39%). Table. - Survival ≥12mo <12mo P n 26 109 Median age 56 (20-79) 57 (21-83) n.s. Male 15 (71%) 73 (65%) n.s. IPI high/high-i @ LD 11 (42%) 62 (57%) n.s. LDH >N @ LD 12 (46%) 68 (62%) n.s. ZUMA1 ineligible 19 (73%) 104 (95%) 0.0019 Bridging responders / no bridging 15 (58%) 28 (27%) 0.0047 ECOG ≥2 @ LD 1/24 (4%) 17/103 (17%) n.s. ≥3 Treatment lines 24 (92%) 76 (70%) 0.023 Prior SCT 7 (27%) 34 (31%) n.s. Tisa-cel 15 (58%) 71 (65%) n.s REL after CAR-T ≤30d 1 (4%) 26 (24%) 0.027 REL after CAR-T >100d 12 (46%) 22 (20%) 0.011 alloHCT performed 13 (50%) 26 (24%) 0.015 1st salvage Pola-based 9 (35%) 30 (28%) n.s. 1st salvage CPi-based 4 (15%) 8 (7%) n.s. 1st salvage Lena-based 1 (4%) 7 (6%) n.s. Image:Summary/Conclusion: Long-term survival after failure of CAR-T therapy for LBCL is possible in about 20% of the patients. Predictors of a favorable survival post REL are good-risk pre CAR-T features and a long interval between CAR-T therapy and REL. AlloHCT can successfully consolidate salvage treatment responses in a sizable proportion of patients and may improve outcome of CAR-T failure.